Emulsions including surface-modified organic molecules

ABSTRACT

The invention is related to emulsions containing surface-modified organic molecules, organic polymeric microspheres, or combinations thereof.

CROSS REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. application Ser. No.10/335,495, filed Dec. 31, 2002, now allowed, the disclosure of which isherein incorporated by reference.

BACKGROUND

This invention relates to liquid-in-liquid emulsions.

Traditional emulsions are made up of two phases: a dispersed phase and acontinuous phase. The most common emulsions consist of only two liquids,water and oil. An o/w (oil-in-water) emulsion consists of oil dropletsdispersed in a continuous aqueous phase, and a w/o (water-in-oil)emulsion consists of water droplets dispersed in oil. Multiple emulsionsmay be formed, for example, when water droplets in a continuous oilphase themselves contain dispersed oil droplets. Emulsification consistsof the break-up of large droplets into smaller droplets due to shearforces. Typically, emulsifiers are used to stabilize emulsions through areduction in interfacial tension. Increasing the viscosity of thecontinuous phase may also prevent phase separation of emulsions.

SUMMARY

In one aspect, the invention provides an emulsion that comprises aliquid continuous phase comprising surface-modified organic molecules,and a dispersed liquid phase. The organic molecules are selected fromsurface-modified fullerenes, surface-modified dendrimers, andcombinations thereof.

In another aspect, the invention provides an emulsion that comprises aliquid continuous phase comprising organic polymeric microspheres, and adispersed liquid phase.

In another aspect, the invention provides multiple emulsions whereineach liquid phase that contains a dispersed liquid phase containssurface-modified organic molecules or organic polymeric microspheres, ora combination of both.

DETAILED DESCRIPTION

The emulsions of the invention are liquid-in-liquid dispersions oremulsions. The stabilized emulsions comprising a continuous phase and adispersed phase are rendered by incorporation of an effective amount ofsurface-modified organic molecules into the continuous phase of thecomposition. The surface-modified molecules maintain the emulsionwithout reducing surface tension at the continuous-dispersed phaseinterface.

In another embodiment, the emulsions of the invention consistessentially of a continuous liquid phase and a dispersed liquid phaseand surface-modified organic molecules or organic polymeric microspheresincorporated in the continuous phase.

The emulsions of the invention may be free of traditional surfactants,detergents, proteins, and emulsifiers and other compounds that stabilizeemulsions through a reduction in surface tension. The emulsions of theinvention are typically stable from days to years under constanttemperature.

The emulsions of the invention may be oil-in-water or water-in-oilemulsions (as those terms are generally defined in the art) or multipleemulsions. An example of a multiple emulsion is an oil-in-water emulsion(dispersed phase) in an oil continuous phase or the opposite multipleemulsion. For multiple emulsions of the invention, different types ofsurface-modified organic molecules or organic polymeric microspheres areor may be needed for each phase that contains another dispersed phase.

The surface-modified organic molecules and organic polymericmicrospheres stabilize emulsions without lowering the surface tension atthe interface between the dispersed and continuous phases. It istheorized that the surface-modified organic molecules or organicpolymeric microspheres become situated between the dispersed phasedroplets in increasing concentration as the liquid continuous phasedrains from between the dispersed phase droplets. The increasedconcentration of surface-modified organic molecules between thedispersed phase droplets prevents the dispersed droplets from contactingone another and coalescing.

The surface-modified organic molecules are substantially soluble in thecontinuous phase. The molecules may be directly soluble in thecontinuous phase or a soluble derivative of a precursor molecule may beprepared, for example, by alkylation. The surface-modified organicmolecules and organic polymeric microspheres are selected to becompatible with the continuous phase.

One useful method of assessing the compatibility of the surface-modifiedorganic molecules and organic polymeric microspheres with the continuousphase includes the step of combining the surface-modified organicmolecules and/or organic polymeric microspheres and the continuous phaseand observing whether the surface-modified organic molecules and/ororganic polymeric microspheres appear to dissolve in the continuousphase.

Specific examples of useful surface-modified organic molecules includealkylated buckminsterfullerenes (fullerenes) and alklylatedpolyamidoamine (PAMAM) dendrimers. Specific examples of fullerenesinclude C₆₀, C₇₀, C₈₂, and C₈₄. Specific examples of PAMAM dendrimersinclude those of Generations 2 through 10 (G2-G10), available fromAldrich Chemical Company, Milwaukee, Wis. PAMAM dendrimers are currentlycommercially available with primary amine, hydroxyl, carboxylate sodiumsalt, mixed amine/hydroxyl, and C₁₂ surface functional groups. The alkylgroups on the organic molecules may be straight or branched and mayrange from at least C₃ to not greater than C₃₀ and may be any size orrange in between C₃ and C₃₀. For example, the ranges may be C₃ to C₂₂;C₃ to C₁₈; C₃ to C₁₂; or C₃ to C₈, and any combination or integertherebetween. The surface-modified organic molecules may be present inthe continuous phase at a level of from at least 0.1 percent by weight.

Specific examples of a useful organic polymeric microspheres includemicrospheres that comprise polystyrene, available from BangsLaboratories, Inc., Fishers, Ind., as powders or dispersions. Averageparticle sizes of the polystyrene microspheres range from at least 20 nmto not more than 60 nm. Current commercially available average particlesizes are 20, 30, 50, and 60 nm. The organic polymeric microspheres maybe present in the continuous phase at a level of from at least 0.1percent by weight.

The emulsions of the invention have a liquid continuous phase. Thecontinuous phase may be made up of one or more miscible or solubleconstituents so long as the dispersed phase may be dispersed in all ofthe constituents of the continuous phase.

Example continuous phases include water, organic liquids including,e.g., acids, alcohols, ketones, aldehydes, amines, amides, esters,glycols, ethers, hydrocarbons, halocarbons, monomers, oligomers,lubricating oils, vegetables oils (including mono- di, andtri-glycerides), silicone oils, moisturizing oils (e.g., mineral andjojoba oils), fuel oils, fuels (including kerosene, gasoline, dieselfuel), oligomers of ethylene glycol, alkyl and aryl nitro compounds,partially or fully fluorinated compounds, and polymers.

The emulsions of the invention have a liquid dispersed phase that isdispersed within the continuous liquid phase. The liquid dispersed phasemay comprise one or more liquids that are miscible or soluble and thatare dispersed within the liquid continuous phase. Examples of suitableliquid dispersed phases include water and all of the organic materialslisted above for use as a continuous phase.

The emulsions of the invention may also contain surface-modifiednanoparticles in combination with surface-modified organic molecules andorganic polymeric microspheres. Surface-modified nanoparticles aredescribed in U.S. Publication No. 2002-0128336-A1, incorporated hereinby reference for the description of the surface-modified inorganicnanoparticles.

Each phase may also contain other dissolved or soluble compounds orcomponents which are added to achieve a desired effect, for example,salts, drugs, dyes, flame retardants, and the like.

The emulsions of the invention are generally made by blending the phasesand mixing. Another way to make the emulsions of the invention is toblend the surface-modified organic molecules or organic polymericmicrospheres, or combinations thereof with the continuous phase (orother phases in the case of multiple emulsions) and then adding thedispersed phase with agitation.

The emulsions of the invention may be useful in foods, cosmetics,pharmaceuticals, and the like.

The invention will now be described further by way of the followingexamples.

EXAMPLES

All solvents and reagents were obtained from Aldrich Chemical Company,unless otherwise noted. All percents and amounts are by weight unlessotherwise specified.

Preparation of Octyl-substituted STARBURST® Dendrimer, Generation 2(Octyl-SG-2)

A 50 mL round-bottom flask was charged with 0.74 g (0.23 mol) ofSTARBURST® (PAMAM-OH) Dendrimer, Generation 2 (obtained from AldrichChemical Co.). N,N-Dimethylformamide (10 g) and triethylamine (0.37 g;0.0036 mol) were added to the flask and the mixture was magneticallystirred until the dendrimer was dissolved. Octanoyl chloride (0.59 g;0.0036 mol) was added to the flask dropwise via syringe over a period ofabout 5 minutes. The mixture was stirred at room temperature for about 2hours, after which water (20 g) was added to the flask. The mixture wasstirred at room temperature overnight. The reaction mixture was pouredinto a separatory funnel and was extracted with toluene (20 g). Thephases were separated and the aqueous phase was extracted two more timeswith toluene (10 g each time). The combined toluene extractsconcentrated to dryness using a rotary evaporator. The resultantorange-brown solid was dried in a vacuum oven at 60° C. and 250 mm Hgpressure for 3 hours. The dry solid was then dissolved in about 30 g oftoluene. This solution was filtered through a 0.2 micrometer syringefilter (Gelman ACRODISC syringe filter, Waters Corp., Milford, Mass.) toafford a clear yellow solution. The toluene solution was concentrated todryness on a rotary evaporator to give 1.13 g of an orange-brown solid.Analysis of the solid by nuclear magnetic resonance spectrometryindicated complete esterification of the hydroxyl groups.

Preparation of Octyl-substituted STARBURST® Dendrimer. Generation 4(Octyl-SG-4)

A 50 mL round-bottom flask was charged with 0.33 g (0.023 mol) ofSTARBURST® (PAMAM-OH) Dendrimer, Generation 4 (obtained from AldrichChemical Co.). N,N-Dimethylformamide (10 g) and triethylamine (0.15 g;0.0015 mol) were added to the flask and the mixture was magneticallystirred until the dendrimer was dissolved. Octanoyl chloride (0.24 g;0.0015 mol) was added to the flask dropwise via syringe over a period ofabout 5 minutes. The mixture was stirred at room temperature for about 2hours, after which water (20 g) was added to the flask. The mixture wasstirred at room temperature overnight. The reaction mixture was pouredinto a separatory funnel and was extracted with toluene (20 g). Thephases were separated and the aqueous phase was extracted two more timeswith toluene (10 g each time). The combined toluene extractsconcentrated to dryness using a rotary evaporator. The resultantorange-brown solid was dried in a vacuum oven at 60° C. and 250 mm Hgpressure for 3 hours. The dry solid was then dissolved in about 30 g oftetrahydrofuran. This solution was filtered through a 0.2 μm syringefilter (Gelman ACRODISC syringe filter) to afford a clear yellowsolution. The tetrahydrofuran solution was concentrated to dryness on arotary evaporator to give 0.48 g of an orange-brown solid. Analysis ofthe solid by nuclear magnetic resonance spectrometry indicated completeesterification of the hydroxyl groups.

Preparation of Octyl-Substituted C₆₀ (Octyl-C₆₀)

A 50 mL round-bottom flask was dried by passing a stream of nitrogen gasthrough it while heating the flask with a gas flame. After the flask hadcooled, it was charged with 10 mL of dry tetrahydrofuran and 0.1 g C₆₀,and the solution was then deoxygenated by briefly bubbling dry nitrogengas through it. A solution of octylmagnesium iodide in diethyl ether (20mL) was added to the flask via syringe as the solution was magneticallystirred. The dark reaction mixture was allowed to stir under nitrogenatmosphere for 7 hours, after which time an additional 5 mL of thesolution of octylmagnesium iodide was added to the flask via syringe.After an additional 16 hours, 10 mL of a 5% aqueous solution of Na₂S₂O₃was added to the flask and the mixture was allowed to stir for 1 hour.The heterogeneous mixture was transferred to a separatory funnel and theorganic phase was separated from the aqueous phase. This organic phasewas dried in a glass dish at 70° C. to afford 0.28 g of a dark solid.Mass spectrometric analysis indicated that the solid was a mixture ofcompounds corresponding to the formula C₆₀(C₈H₁₇)_(n) where n=1 to 17and where the average value of n is 11.

Stabilization of Water-in-Oil Emulsions

Solutions or dispersions of the surface-modified STARBURST® dendrimerswere made in toluene, at the concentrations specified in Table 1, bycombining, in screw-cap glass vials, the calculated amount of thecompounds and 2 mL of toluene. When the compounds were, or appeared tobe, dissolved, 1 g of the toluene solution and 1 g of water werecombined in a screw-cap glass vial, the vial was capped, and was thenshaken vigorously by hand for 15 seconds. The emulsions that formedcomprised less than 50 volume percent water, as evidenced by theseparation of a homogeneous water phase from the emulsion phase.Octyl-C₆₀ was dissolved in toluene to give 3 g of a 2% solution. Thiswas combined with 3 g of water in a screw cap vial, and theemulsification was carried out as described above. The data are given inTable 1. TABLE 1 Example Emulsifying Agent Concentration EmulsionComparative 1 None N/A No Comparative 2 C₆₀ 2% No 1 Octyl-SG-2 2% Yes 2Octyl-SG-4 2% Yes 3 Octyl-C₆₀ 2% YesStabilization of Oil-in-Water Emulsions

Solutions or dispersions of 20 nm, 30 nm, 50 nm and 60 nmsurface-modified polystyrene microspheres (available from BangsLaboratories, Inc., Fishers, Ind.) were made in water at a concentrationof 2%. When the compounds were, or appeared to be, dissolved, 1 g of theaqueous solution and 1 g of toluene were combined in a screw-cap glassvial, the vial was capped and was then shaken vigorously by hand for 15seconds. The emulsions that formed comprised less than 50 volume percenttoluene, as evidenced by the separation of a homogeneous toluene phasefrom the emulsion phase. The data are given in Table 2. TABLE 2 ExampleEmulsifying Agent Emulsion 4 20 nm polystyrene microspheres Yes 5 30 nmpolystyrene microspheres Yes 6 50 nm polystyrene microspheres Yes 7 60nm polystyrene microspheres Yes

All patents, patent applications, and publications cited herein are eachincorporated by reference, as if individually incorporated. Foreseeablemodifications and alterations of this invention will be apparent tothose skilled in the art without departing from the scope and spirit ofthis invention. This invention should not be restricted to theembodiments that are set forth in this application for illustrativepurposes.

1. An emulsion comprising: a continuous liquid phase comprising aplurality of surface-modified dendrimers, dispersed in said continuousphase; and a dispersed liquid phase dispersed in said continuous phase.2. The emulsion of claim 1 wherein the continuous phase comprises anorganic liquid.
 3. The emulsion of claim 1 wherein the emulsion is freeof surfactant.
 4. The emulsion of claim 1 wherein the continuous phaseis selected from the group consisting of water, alcohols, aldehydes,ketones, esters, ethers, amines, amides, hydrocarbons, halocarbons,monomers, oligomers, lubricating oils, vegetable oils, silicone oils,moisturizing, fuel oils, fuels, oligomers of ethylene glycol, alkyl andaryl nitro compounds, partially or fully fluorinated compounds, andpolymers and mixtures thereof.
 5. The emulsion of claim 1 wherein thesurface-modified organic molecules comprise alkyl surface groups.
 6. Theemulsion of claim 5 wherein the alkyl groups are at least C₃.
 7. Theemulsion of claim 5 wherein the alkyl groups are not greater than C₃₀.8. The emulsion of claim 5 wherein the alkyl groups range from C₃ toC₂₂.
 9. The emulsion of claim 5 wherein the alkyl groups range from C₃to C₁₈.
 10. The emulsion of claim 5 wherein the alkyl groups range fromC₃ to C₁₂.
 11. The emulsion of claim 5 wherein the alkyl groups are C₃to C₈ and any combination or integer therebetween.
 12. The emulsion ofclaim 1 wherein the dendrimers are G2, G3, G4, G5, G6, G7, G8, G9, orG10 dendrimers, or combinations thereof.
 13. The emulsion of claim 1wherein the dispersed phase is selected from the group consisting ofwater, alcohols, aldehydes, ketones, esters, ethers, amines, amides,hydrocarbons, halocarbons, monomers, oligomers, lubricating oils,vegetable oils, silicone oils, moisturizing, fuel oils, fuels, oligomersof ethylene glycol, alkyl and aryl nitro compounds, partially or fullyfluorinated compounds, and polymers and combinations of any of these.14. The emulsion of claim 1 wherein the organic molecules are a mixtureof fullerenes and dendrimers.
 15. The emulsion of claim 1 wherein thecontinuous phase comprises an organic liquid.
 16. The emulsion of claim1 wherein the continuous phase further comprises surface-modifiedinorganic nanoparticles.
 17. The emulsion of claim 1 dispersed within asecond continuous phase.